Epidemiology and Burden Major Depressive Disorder MDD Depression

Epidemiology and Burden Major Depressive Disorder (MDD)

Depression is a highly prevalent disorder Depression is a chronic, recurring, and progressive disorder affecting 300 -350 million people worldwide 1, 2 • The percentage of people suffering from MDD worldwide was 4. 4% (4. 1– 4. 7%) in 2010. 2 • The prevalence of MDD remained very consistent between 1990 (4. 4% (95% uncertainty: 4. 2– 4. 7%)), 2005 (4. 4% (4. 1– 4. 7%) and 2010. • Prevalence in 2010 was higher in females at 5. 5% (5. 0– 6. 0%) compared to males at 3. 2% (3. 0– 3. 6%). 2 • Across the lifespan, prevalence of MDD increases steadily between 3 and 19 years; peaks between 20 and 64 years; decreased between 65 to 74 years. (1) Depression. Factsheet no. 369. Available at: http: //www. who. int/mediacentre/factsheets/fs 369/en/. Accessed April 2016. (2) Ferrari AJ, et al. 2010. PLo. S One. 2013 a; 8(7): e 69637

Depression is a highly prevalent disorder It is estimated that each year, 6. 9% of the EU population suffers from MDD 1 The lifetime prevalence of MDD is 6. 5– 21%, depending on the country 2 -4 MDD 6. 5 – 21 % Mean lifetime prevalence of major depressive episode 4 Netherlands 18. 5% Germany 9. 8% Ukraine Belgium 14. 5% 14% France 21% Italy Spain Lebanon 9. 8% 11% Israel 11. 2% 10% USA 19% Mexico 8% Shenzen, China 7% India 9% Colombia 13% 5– 10% Japan 9. 8% Brazil 18. 8% >10– 15% >15– 20% South Africa 9. 7% >20% *Total high income countries = 14. 6%; total low to middle income countries = 11. 1% Only data for countries in the WHO study are presented (1) Wittchen HU et al. Eur Neuropsychopharmacol 2011; 21: 655 -79; (2) Hasin DS et al. Arch Gen Psychiatry 2005; 62: 1097 -106; (3) Kessler RC et al. Arch Gen Psychiatry 2005; 62: 593 -602; (4) Bromet E et al. BMC Med 2011; 9: 90 New Zealand 7%

12 month prevelance of mental disorders in Europe in 2011# 0. 4 (1. 0) 0. 7 (2. 9) 0. 9 (3. 0) 0. 9 (1. 5) 1. 0 (4. 2) 1. 0 (1. 4) 1. 2 (5) 1. 3 (4. 3) 2. 0 (7. 7) 3. 0 (2. 1) 3. 4 (14. 6) Opioid dependence OCD Bipolar disorder Eating disorder Mental retardation Cannabis dependence Psychotic disorders Personality disorders PTSD Conduct disorder Alcohol dependence Somatoform disorders ADHD Major depression Anxiety disorders 4. 9 (20. 4) 5. 0 (3. 3) 6. 9 (30. 3) 14 (61. 5) 0 2 4 6 8 10 12 12 -month prevalence in percent (no. persons affected) Prevalence ”best estimate”, conducted in EU-27 countries, plus Iceland, Norway and Switzerland * More details available in the speaker notes # Wittchen, H. -U. et al, 2011. Eur. Neuropsychopharmacology (2011) 21, 655– 679 14

Burden of Major Depressive Disorder (MDD)

” “Depression is the leading cause of disability worldwide, and is a major contributor to the overall global burden of disease” WHO Fact Sheet No. 369 - Reviewed April 2016

MDD is a leading cause of burden • MDD has a worldwide prevalence estimate of 4. 4%1 Ten leading causes of YLDs worldwide, Global Burden of Disease Study 20104 Disorder • MDD is the second leading cause of years lived with disability (YLDs)2 • The Global Burden of Disease Study 2010 found that MDD accounted for 8. 2% of global YLDs • Unipolar depressive disorders are predicted to become the leading cause of burden (DALYs) by 20303 Rank Lower back pain 1 Major depressive disorder 2 Iron-deficiency anaemia 3 Neck pain 4 COPD 5 Other musculoskeletal disorders 6 Anxiety disorders 7 Migraine 8 Diabetes 9 Falls 10 COPD=chronic obstructive pulmonary disease DALY=disability-adjusted life-year (1) Ferrari AJ, et al. 2010. PLo. S One. 2013; 8(7): e 69637; (2) Ferrari et al. PLo. S Med 2013; 10(11): e 1001547; (3) WHO. Global burden of mental disorders and the need for a comprehensive, coordinated response from health and social sectors at the country level. 2011. Retrieved from: http: //apps. who. int/gb/ebwha/pdf_files/EB 130/B 130_9 -en. pdf. Accessed April 2016; (4) Vos et al. Lancet 2012; 380: 2163– 2196.

Contribution of Non-communicable diseases disability-adjusted life years By 2013, depression is projected to be the largest contributor to the global burden of disease 1 Digestive Disorders Musculoskeletal Disorders 4% 6% Rispiratory Disease Endocrine 8% 4% Other Non-communicable Diseases 7% Unipolar Affective Dis 10% Sense Organ Impairement 10% Neuropsychiatric Disorders 29% Schizophrenia 2% Bipolar Affective Dis 2% Dementia 2% Substance-use Dis 4% Other Mental Dis 3% Epilepsy 1% Other Neurol Dis 2% Cardiovascular Disease 22% Other Neuropsych Dis 3% Cancer 11% Dis = Disorder/s; Neurol = Neurologic; Neuropsych = Neuropsychiatric Prince et al. Lancet 2007; 370: 859– 877

The burden associated with depression is large and increasing Health-adjusted life years (HALYs) - A combination of years lived with less than full function and years lost to early death. 1 Depression Bipolar Disorder Alcohol Schizophrenia Years of reduced function 0 50 100 150 Years of life lost 200 250 In terms of disability-adjusted life-years lost, depression is the most burdensome disorder of all brain diseases in the EU 2 (1) Ratnasingham S et al. Opening Eyes, Opening Minds: The Ontario Burden of Mental Illness and Addictions Report. Institute for Clinical Evaluative Sciences and Public Health Ontario, 2012; (2) Wittchen HU et al. Eur Neuropsychopharmacol 2011; 21: 655 -79

Depression is the most burdensome disorder of all brain diseases in the EU Rankings of DALY estimates (age 15+) by selected mental and neurological disorders for the EU-27 population Rank Men Diagnosis Women Total DALYs* Diagnosis Both Total DALYs* Diagnosis Total DALYs* 1 Alcohol Use Disorders 1669 k Major Depression 2892 k Major Depression 4320 k 2 Major Depression 1428 k Dementias 1477 k Dementias 2237 k 3 Stroke 783 k Stroke 793 k Alcohol Use Disorders 2040 k 4 Dementias 760 k Migraine 491 k Stroke 1577 k * Total DALYs in thousands(k) DALYs = disability-adjusted life-years lost Major depression contributes 7. 2% of the overall burden of disease in Europe, making it the number 1 contributor directly before Alzheimer's disease/dementia and alcohol use disorders. 2) Wittchen HU et al. Eur Neuropsychopharmacol 2011; 21: 655 -79

Depression has detrimental effects on overall health Mean Health Score (0– 100) 100 90. 6 79. 6 80. 3 79. 3 78. 9 72. 9 80 67. 1 65. 8 71. 8 65. 4 58. 5 56. 1 60 40 Depression adds to the burden of asthma, angina, arthritis, or diabetes 20 0 ion No nic ro h c co it nd As th o ma nly g An o ina s nd ma tes dition h e t n a ns b o s n i a a a i s io co e d res ndit nd d d onic ab nd an p sio a n a e o s a Di n n D ic c n hr e sio n sio ion 2 c pr sio s s ≥ s s e e e s hro r e re c pr D p r p e 2 p ≥ D De De De nly thr Ar o itis o tes nly ly n no itis hr art a in ng Depression is associated with poorer overall health scores than arthritis or diabetes and significantly adds to the burden of other chronic conditions Adapted from Moussavi S, et al. Lancet. 2007; 370: 851 -8.

Depression is associated with significant personal and societal consequences Decreased ability to interact with friends, family, and colleagues 1, 3 High morbidity and mortality 2, 3 The leading cause of psychiatric disability worldwide 2, 3 3, 000 suicide deaths every day, worldwide 3 1 in 20 people reported having an episode of depression in the previous year 3 Largely driven by workplace productivity losses 2 (1) American Psychiatric Association. Diagnostic and Statistical Manual of Mental Health Disorders. 5 th ed. Washington, DC: American Psychiatric Association; 2013; (2) Krol M, et al. Pharmacoeconomics. 2011; 29(7): 601– 19; (3) Marcus M, et al. 2012. http: //www. who. int/mental_health/management/depression/who_paper_depression_wfmh_2012. pdf? ua=1 Accessed April 16, 2014. Severe economic burden for patients and society 2

The personal burden of MDD can be significant and wide-ranging Marital dissatisfaction/discord and negative parenting behaviours are strongly related to symptoms of depression 1 MDD is significantly associated with chronic physical disorders including arthritis, asthma, cancer, diabetes, cardiovascular disease and pain 1 Family Finances Personal earnings and household income of people with MDD are substantially lower than those without depression 1 1. Kessler RC. Psychiatr Clin North Am 2012; 35(1): 1– 14. 2 Physical health Work performance People with MDD have the highest number of days away from work of any physical or mental disorder 1

MDD has significant costs to society Predicted to be leading cause of disease burden by 20301 98. 7 million Percentage of the global burden of disease (DALYs) represented by depression in 20042 Estimated number of people with moderate or severe disability due to depression in 20042 4. 3% 1. 4 x 2 nd Leading cause of years lived with disability in 20133 Increased risk of mortality for people with depression compared with the general population 1 53% Median percentage increase in disability associated with depression 1990– 20133 (1) WHO. Global burden of mental disorders and the need for a comprehensive, coordinated response from health and social sectors at the country level. 2011. Retrieved from: http: //apps. who. int/gb/ebwha/pdf_files/EB 130/B 130_9 -en. pdf. Accessed April 2016; (2). WHO The Global Burden of Disease 2004 Update. http: //www. who. int/healthinfo/global_burden_dis ease/2004_report_update/en/. Accessed April 2016. 3. Global Burden of Disease Study 2013 Collaborators. Lancet 2015; 386(9995): 743– 800

MDD has significant costs to society: EU € 92 billion* Percentage of the cost of depression comes from workplace absenteeism and presenteeism 1 Estimated costs of depression 1 € 54 billion* 50% Percentage of patients being treated for depression who take employment sick leave 1 Non-healthcare-related costs of depression in 2010 (e. g. loss of work productivity)1 >⅓ Proportion of patients on employment sick leave taking over 26 weeks off work 1 (1) Hughes S. MEP: Depression in the Workplace. http: //www. enwhp. org/fileadmin/user_upload/pdf/Policy_recommendations_depression_at_the_workplace. pdf. Accessed July 2015

Depression is associated with significant economic costs • Major depression is the leading cause of global disease burden among mental, neurological and substance-use disorders 1 • The total annual cost of depression in Europe was estimated at € 118 billion in 2004, which corresponds to a cost of € 253 per inhabitant 2 • $44 billion cost to US employers in 1 year 3 Burden of disease (DALYs): Leading causes in high-income countries 1. Majordepressivedisorders disorder 1. Unipolar 8. 2 6. 3 2. Ischaemic heart disease 6, 3% (7, 7) 3. 9 3, 9% (4, 8) 3. Cerebrovascular disease 3. 6 3, 6% (4, 4) 4. Alzheimer and other dementias 5. Alcohol use disorders 3. 4 3, 4% (4, 2) 6. Hearing loss, adult onset 3. 4 3, 4% (4, 2) 7. COPD 3 3, 0% (3, 7) 8. Diabetes mellitus 3 3, 0% (3, 7) 9. Trachea, bronchus, lung cancers 3 3, 0% (3, 6) 2. 6 2, 6% (3, 1) 10. Road traffic accidents 0 DALY, disability-adjusted life-year; COPD, chronic obstructive pulmonary disease 8, 2% (10) 2 4 6 8 Percent of total DALYs (million DALYs) 10 (1) Collins PY, et al. Nature. 2011; 475: 27– 30; (2) Sobocki P, et al. J Ment Health Policy Econ. 2006; 9: 87 -98; (3) Stewart WF, et al. JAMA. 2003; 289: 313544; (4) World Health Organization. Available at: http: //www. who. int/healthinfo/global_burden_disease/GBD_report_2004 update_part 4. pdf? ua = 1. Accessed June 2016

Cost per patient of brain disorders in Europe in 2010# #27 Headache 285 Eating disorders 559 790 Sleep disorders Somatoform disorder 1037 Anxiety disorders 1077 Mood Disorders* Mood disorders 3406 Child/Adolescent. . . 3595 Addiction 4227 Epilepsy 5221 Personality disorders 6328 Stroke 7775 Traumatic Brain Injury 8809 Mental Retardation 10334 Parkinsons disease 11153 Dementia Psychotic disorders Brain tumor Multiple sclerosis Neuromuscular. . . 0 5000 10000 16584 18796 21590 26974 30052 15000 20000 Cost per patient (€ PPP 2010) * Mood disorders includes major depression and (prevalence 6. 9%) and bipolar (prevalence 0. 9%) PPP = purchasing power parity Gustavsson et al. , Eur Neuropsychopharm (2011)21, 718 -779 EU countries plus Switzerland, Norway, and Iceland 25000 30000 35000

Cost per patient of mental disorders in Europe in 2010# #27 EU countries plus Switzerland, Norway, and Iceland 559 Eating disorders Somatoform disorder 1037 Anxiety disorders 1077 Mood disorders Disorders* 3406 Child/Adolescent disorders 3595 Addiction 4227 Personality disorders 6328 Mental Retardation 10334 Psychotic disorders 18796 0 2000 4000 6000 8000 10000 12000 Cost per patient (€ PPP 2010) * Mood disorders includes major depression and (prevalence 6. 9%) and bipolar (prevalence 0. 9%) PPP = purchasing power parity Gustavsson et al. , Eur Neuropsychopharm (2011)21, 718 -779 14000 16000 18000 20000

Number of persons with disorders of the brain in Europe 2010 # #27 Brain Tumor 0. 2 Neuromuscular. . . 0. 3 Multiple Sclerosis 0. 5 Parkinson's disease 1. 2 Eating disorders 1. 5 Epilepsy 2. 6 Traumatic Brain Injury 3. 7 Mental Retardation 4. 2 Personality disorders 4. 3 Psychotic disorders 5 Child/Adolescent. . . 5. 9 Dementia 6. 3 Stroke 8. 2 Addiction 15. 5 Somatoform disorder 20. 4 Mood Disorders* Mood disorders Sleep disorders Anxiety disorders Headache 0 20 EU countries plus Switzerland, Norway, and Iceland 33. 3 44. 9 69. 1 152. 8 40 60 80 100 120 Number of diagnoses in million * Mood disorders includes major depression and (prevalence 6. 9%) and bipolar (prevalence 0. 9%) Gustavsson et al. , Eur Neuropsychopharm (2011)21, 718 -779 140 160 180

Mood disorders bears the highest total costs of brain disorders in Europe 2010# #27 Eating disorders 827 Brain tumor 5174 7726 Neuromuscular. . . Epilepsy 13800 Parkinsons disease 13933 Multiple sclerosis 14559 Somatoform disorder 21169 Child/Adolescent. . . 21326 Personality disorders 27345 Traumatic brain injury 33013 Sleep disorders 35425 Mental Retardation 43301 Headache 43514 Stroke Addiction Anxiety disorders Psychotic disorders Dementia Disorders* Mood disorders 0 20000 40000 EU countries plus Switzerland, Norway, and Iceland 64053 65684 74380 93927 105163 113405 60000 80000 Total cost per disorder (million € PPP 2010) * Mood disorders includes major depression and (prevalence 6. 9%) and bipolar (prevalence 0. 9%) PPP = purchasing power parity Gustavsson et al. , Eur Neuropsychopharm (2011)21, 718 -779 100000 120000

Mood disorders bears the highest total costs of mental disorders in Europe 2010# #27 EU countries plus Switzerland, Norway, and Iceland 827 Eating disorders Somatoform disorder 21169 Child/Adolescent disorders 21326 Personality disorders 27345 43301 Mental Retardation Addiction 65684 Anxiety disorders 74380 Psychotic disorders 93927 Mood disorders Disorders* 0 113405 20000 40000 60000 80000 Total cost per disorder (million € PPP 2010) * Mood disorders includes major depression and (prevalence 6. 9%) and bipolar (prevalence 0. 9%) PPP = purchasing power parity Gustavsson et al. , Eur Neuropsychopharm (2011)21, 718 -779 100000 120000

1. 00 Cognitive problems 0. 80 Core symptoms: depressed mood/ diminished interest Lack of energy 0. 60 Sleeping problems Worthlessness/guilt 0. 40 Eating problems 0. 20 Psychomotor problems 0. 00 7 5 14 13 9 12 3 1 12 11 5 10 97 89 73 57 81 65 49 41 33 25 17 9 Death ideations 1 Mean Proportion of Time DSM-IV Symptom Cluster Is Present Depressive symptoms persist during periods of remission and subsequent depressive episodes Weeks of Follow-up Mean proportion of time symptoms are present during 3 -year follow-up period (N=267) Conradi HJ, et al. Psychol Med. 2011; 41: 1165– 1174.

Cognitive impairment is among the most common residual symptoms in MDD* Persistent depressive symptoms in STAR*D responders Symptoms present in patients with MDD who responded but did not remit (N=428) Mc. Clintock SM, et al. J Clin Psychopharmacol. 2011; 31: 180 -6.

Patients with cognitive symptoms of depression often have deficits in overall functioning 1, 2 Learning Attention Motor Skills Deficits in almost every domain of cognitive functioning 2 Verbal knowledge Non-Verbal knowledge Episodic Memory Working Memory Processing Speed Deficits associated with functional domains 2 Executive Functioning Work Family Life Social Interaction Cognitive deficits are clinically important 1, 3 (1) Marazziti D, et al. Eur J Pharmacol. 2010; 626: 83 -86; (2) Millan MJ, et al. Nat Rev Drug Discov. 2012; 11: 141 -168; (3) American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA: APA 2013.

Depression costs more to employers than is spent on managing it Depression costs for employers in selected regions: € 7. 5 billion in € 37 billion Australia 3 in the US 2 € 54 billion in the EU 1 Direct medical costs of managing depression in the EU: € 38 billion 1 (1) Olesen J, et al. Eur J Neurol. 2012; 19: 155– 162. (2) Stewart WF, et al. JAMA. 2003; 289(23): 3135– 3144. (3) Perkins M, Back A. Mental health failing costs business $11 b. 2014. Retrieved from: http: //www. smh. com. au/national/mental-healthfailing-costs-business-11 b-20140519 -38 k 5 r. html. Accessed May 2015

Depression directly impacts working time One out of 10 people have taken time off work for depression Taken an average of 36 days period IDEA: Impact of Depression at Work in Europe Audit Final report. Ipsos Healthcare. October 2012.